Late life depression (LLD) is a common and debilitating problem that may indicate a higher risk for developing cognitive impairment. Our current grant "Treatment Outcome of Vascular Depression" MH60697 has gathered a large sample (n=120) of LLD patients and controls (n=40) to examine white matter disease, cerebrovascular risk factors and cognitive function prospectively. However, LLD is a heterogeneous disorder with poorly understood risk factors for development; both vascular disease and incipient dementia are common comorbid syndromes. LLD depressive symptoms actually may be the presenting symptoms of incipient dementia. Alternatively, LLD may be an independent risk factor for AD. Thus, incipient dementia, perhaps years in advance of DAT, is an important factor that may contribute to poor outcome, including treatment resistance in LLD. A novel agent for imaging brain amyloid in vivo, [11C] PIB, presents the opportunity to determine whether subjects with LLD have abnormal brain amyloid binding. We have preliminary data showing a 3 fold increase in PIB+ status in LLD: 3/10 LLD patients vs. 2/20 controls were PIB+. Further 2/5 antidepressant non-responders (NR) vs. 1/5 responders (R) were PIB+. In our current proposal, we use PET imaging of [11C] P1B to gather preliminary data to investigate whether compared with control subjects, elevated brain PIB binding will be associated with LLD, especially in LLD treatment non-responders and those with longstanding depression. If this PET data shows support for our hypotheses, we will use this pilot dataset as a basis for a larger grant application to further explore these relationships. We also have a number of other key neuroimaging, cognitive and clinical data from our original "Treatment Outcome" study and will explore the extent to which they provide significant predictive effects for LLD. Nondemented LLD subjects age 65-85 y/o (n=50) who have completed a treatment study with a standard antidepressant (sertraline) will be recruited for imaging with PET and [11C] PIB, MRI, cognitive testing and ascertainment of clinical measures. Depressed subjects who did not respond to treatment (n=25) will be compared with responders (n=25) and with a non-demented non-depressed comparison sample (n=25). AIM1: Compared with controls, LLD subjects will have elevated gray matter [11C] PIB binding. AIM2: Compared with responders, a higher number of non-responders will have elevated gray matter [11C] PIB binding. AIM 3: Additional measures, including lifetime duration of depression, untreated episodes of depression, age of onset and comorbid vascular risk factors will be explored. Successful completion of this study will allow effect size and power calculations critical in designing a definitive study to determine whether LLD is associated with increased numbers of PIB+ patients. [unreadable] [unreadable] [unreadable] [unreadable]